CN101400708A - Method for the purification of resorbable polymers from residual monomers - Google Patents
Method for the purification of resorbable polymers from residual monomers Download PDFInfo
- Publication number
- CN101400708A CN101400708A CNA2007800071700A CN200780007170A CN101400708A CN 101400708 A CN101400708 A CN 101400708A CN A2007800071700 A CNA2007800071700 A CN A2007800071700A CN 200780007170 A CN200780007170 A CN 200780007170A CN 101400708 A CN101400708 A CN 101400708A
- Authority
- CN
- China
- Prior art keywords
- polymkeric substance
- lactide
- crit
- concentration
- log
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Granted
Links
Classifications
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F6/00—Post-polymerisation treatments
- C08F6/06—Treatment of polymer solutions
- C08F6/10—Removal of volatile materials, e.g. solvents
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
- C08F6/00—Post-polymerisation treatments
- C08F6/001—Removal of residual monomers by physical means
- C08F6/003—Removal of residual monomers by physical means from polymer solutions, suspensions, dispersions or emulsions without recovery of the polymer therefrom
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/88—Post-polymerisation treatment
- C08G63/90—Purification; Drying
-
- C—CHEMISTRY; METALLURGY
- C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
- C08G—MACROMOLECULAR COMPOUNDS OBTAINED OTHERWISE THAN BY REACTIONS ONLY INVOLVING UNSATURATED CARBON-TO-CARBON BONDS
- C08G63/00—Macromolecular compounds obtained by reactions forming a carboxylic ester link in the main chain of the macromolecule
- C08G63/02—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds
- C08G63/06—Polyesters derived from hydroxycarboxylic acids or from polycarboxylic acids and polyhydroxy compounds derived from hydroxycarboxylic acids
- C08G63/08—Lactones or lactides
Landscapes
- Chemical & Material Sciences (AREA)
- Health & Medical Sciences (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Medicinal Chemistry (AREA)
- Polymers & Plastics (AREA)
- Organic Chemistry (AREA)
- Dispersion Chemistry (AREA)
- Polyesters Or Polycarbonates (AREA)
- Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Addition Polymer Or Copolymer, Post-Treatments, Or Chemical Modifications (AREA)
Abstract
The invention relates to a method for the purification of a resorbable polymer from residual monomers comprising the addition of a solution of said polymer in a solvent and the addition of a precipitation agent into a mixing chamber to precipitate the polymer, characterized in that the concentration of the polymer in the solution is log Ccrit +- 0.3 logarithmic units, wherein Ccrit is the critical concentration.
Description
The present invention relates to a kind of method from the residual monomer purification of resorbable polymers.
US patent 4,810,775 discloses a kind of purification process of resorbable polymers, wherein polymkeric substance is dissolved in the solvent and polymers soln is added in the precipitation agent in the mechanical dispersion unit.Polymkeric substance precipitates and separates with the slurry that comprises described precipitation agent and precipitation polymers.For example, this method produces the polymer poly (D, L-rac-Lactide) of purifying, residual monomer D, and the content of L-rac-Lactide is 0.5wt%, and for D, L-rac-Lactide, glycolide copolymer, residual monomer content still are 0.13-0.3wt%.
Obtain having the polymkeric substance of higher residual monomer content as the method for above-mentioned patent disclosure.Especially when described polymkeric substance was used for the medical science of the mankind or animal and pharmaceutical use, above-mentioned residual monomer content was high as can't to accept.When being used for medical science and pharmaceutical use, polymkeric substance should comprise alap monomer content, does not more preferably have the residual monomer of detectable amount at all, because this impurity can cause the side effect of undesirable and potentially dangerous.The polymkeric substance that is used for these purposes generally includes resorbable polymers, for example can resorbent polyester.The controlled drug that resorbable polymers for example is used for using at human body or animal body discharges and/or dissimilar implants, in suture line and bone fixation element.
Polymkeric substance or polyester based on lactic acid or rac-Lactide and/or oxyacetic acid or glycollide are used in particular in the such use, because described polymkeric substance degrades under the influence of body fluid in human body or animal body, and therefore do not leave a trace.This has prevented from for example to be used for removing from body the needs of the operation second time of described bone fixation element after finishing its purpose.
Residual lactide that for example contains in resorbable polymers or glycolide monomer are with very fast hydrolysis and will form acid.These acid can influence skin or the other parts that efficacy of drugs and/or these acid cause stimulating human body or animal body negatively.In addition, residual monomer can be to being used for medicine, particularly protein-based medicine, and/or in pharmaceutical use, be used for the activeconstituents that controlled drug discharges and have disadvantageous effect.In addition, residual monomer can have the intensive negative effects for the thermostability and/or the physical strength of polymkeric substance, and when polymkeric substance during as the implant of human body or animal body, it in addition can quicken the decomposition or the degraded of polymkeric substance." non-bearing (non-bear ing) " medical implant that rac-Lactide and glycollide based polyalcohol are preferred for needing the medical implant such as the bone fixation element of high mechanical strength and not needing are used for this physical strength is because they are degraded in human body and animal body.When described polymkeric substance comprised a large amount of residual glycollide, oxyacetic acid, rac-Lactide or rac-Lactide acid mono, they can not be used for this class purposes.
The invention provides a kind of method, preferably make residual monomer content be lower than the limit of detection of GC (gas chromatography) from the residual monomer purification of resorbable polymers.The residual monomer content of this strong reduction makes the polymkeric substance that obtains be very suitable for medical science and other purposes, because it will not have above-mentioned side effect.It is found that the separation efficiency decisive role of the kinematic viscosity of this polymkeric substance for polymkeric substance and residual monomer.Find in addition to be positioned at or to approach so-called threshold concentration (C when polymer concentration
Crit) time obtain optimum.
For this reason, the present invention relates to a kind of by making the method for polymer precipitation from the residual monomer purification of resorbable polymers, comprise add described polymkeric substance in solvent solution and in mixing section, add precipitation agent, the concentration that it is characterized in that polymkeric substance in the solution is log C
Crit± 0.3 log unit, wherein C
CritIt is threshold concentration.
Threshold concentration C
CritBe notion very basic in the polymer chemistry, and belong to high molecular scholar's ABC.For example, principle can be referring to the standard school edition (standard student ' sedition of G.Challa) of G.Challa; ＂ Polymeerchemie ＂; Het Spectrum, Utrecht, Antwerpen (Pri sma Technica52); 1973 (96-99 pages or leaves).C
CritBe that wherein segment distributes by the uniform concentration of solution becomes.Under this concentration, single chain no longer has difference.Be higher than C
CritConcentration under, therefore polymers soln comprises the winding polymer chain that can not show separately, has shown as polymkeric substance.C
CritCan measure the graphic representation of polymer concentration logarithm (log c) by drawing kinematic viscosity logarithm (log).Kinematic viscosity can be measured by the known mode of technician, as using the Ubbelohde viscometer.Because kinematic viscosity is at C
CritBelow increase along with concentration more or less, in fact this graphic representation has at cross one another two straight lines of intersection point.This intersection point is log C
CritValue, its form with wt.% concentration provides C
Crit
Polymer concentration according to the present invention is at C
CritAbout.According to the present invention, it is found that for when precipitation from polymkeric substance separating residual monomer, C
Crit0.3 log unit be optimal with interior polymer concentration.More preferably polymer concentration is 0.2 log unit, most preferably C
Crit0.1 log unit in.
The polymkeric substance that is suitable for according to purification process of the present invention is a resorbable polymers, and it is amorphous or high crystalline (have and be higher than 70% degree of crystallinity) or has between the two degree of crystallinity.Can use various purification process to come the resorbable polymers of purified crystals.Purification process according to the present invention is particularly suitable for the resorbable polymers of the unbodied and partial crystallization of purifying, the degree of crystallinity of the resorbable polymers of described partial crystallization is 0-70% and more preferably 0-20%, because find than the known purification methods of the resorbable polymers of described type, this method more effectively, simply and cheaply.In addition, when especially the above-mentioned type polymkeric substance is used for medical usage, therefore need high purification degrees for residual monomer content, this can realize by purification process according to the present invention.
Polyester and more particularly be based on lactic acid or the polyester of rac-Lactide and/or glycol acid or glycollide is preferred for that medical usage such as controlled drug discharge, non-bearing implant and carrying implant be as being used for the bone fixation element of human body or animal body.Described polymkeric substance comprises homopolymer and the homopolymer of rac-Lactide and the other multipolymer or the terpolymer based on rac-Lactide and/or glycollide and/or caprolactone of glycollide.Rac-Lactide comprises L-, D-, meso or D, L-rac-Lactide or its mixture.Other homopolymer and copolymerization/terpolymer based on hydroxycarboxylic acid also is suitable for according to purification process of the present invention.The polymkeric substance of methyl glycollide, dimethyl glycollide, many methyl glycollide, diethyl glycollide, dibutyl glycollide, caprolactone, valerolactone, ten lactones, propiolactone, butyrolactone and pivalolactone or preferably based on their polymkeric substance, and based on trioxane ketone (1,3 and 1,4), diethyleno dioxide ketones (1,3 and 1,4), the polymkeric substance of Qu Dai diethyleno dioxide ketone, trimethylene carbonate, ethylidene carbonic ether and propylene carbonate.Described polymkeric substance also is applied to (medical science) purposes usually, wherein needs utmost point low residual monomer content, does not preferably contain residual monomer.
Other suitable (copolymerization) monomer comprises compound such as tetramethyl glycolide, Xylitol, Sorbitol Powder, Saccharum lactis, adonit, tetramethylolmethane, fructose and/or Epicholorohydrin, the sec.-propyl morpholine, the isopropyl methyl morpholine diketone, β-propynoic acid, Alpha-hydroxy (different) butyric acid, Alpha-hydroxy (different) valeric acid, Alpha-hydroxy (different) caproic acid, Alpha-hydroxy-α-diethyl butyric acid, Alpha-hydroxy-α-Jia Jiwusuan, the Alpha-hydroxy enanthic acid, Alpha-hydroxy is sad, Alpha-hydroxy (four) capric acid and/or Alpha-hydroxy stearic acid.
According to purification process of the present invention, be dissolved in polymkeric substance in the solvent and use precipitation agent precipitation.In mixing section, add polymers soln with mechanical dispersion unit.Described precipitation agent is liquid and/or mixtures of liquids, and wherein polymkeric substance does not dissolve or dissolving hardly, and wherein solvent dissolves.When polymers soln in described mixing section during the contact precipitation agent, solvent and precipitation agent dissolve each other and obtain new solvent or liquid phase, wherein polymkeric substance is separated out owing to its strong solubleness that reduces in liquid phase precipitates.Impurity in the polymkeric substance such as residual monomer dissolve or are retained in the liquid phase, thereby separate with precipitation polymers.The result forms the slurry of described liquid phase and solid phase, and this solid phase comprises the polymkeric substance of precipitation and purifying.
This polymkeric substance can be dissolved in various types of solvents, comprises for example acetone, 1,4-diox, N,N-DIMETHYLACETAMIDE, tetrahydrofuran (THF), toluene, methylformamide, methyl-sulphoxide or hydrochloric ether such as chloroform and methylene dichloride.Preferred solvent is an acetone, because it is of value to environment (for example having good degradation property when wastewater treatment) and is cheap solvent and compares with for example hydrochloric ether based solvent and to have less toxicity.
Suitable precipitation agent is water, methyl alcohol, ethanol, freon, for example as the hydrocarbon of sherwood oil and the mixture and the organic solvent of hydrocarbon, polymkeric substance has utmost point low-solubility therein.Most preferred precipitation agent is a water, because it is cheap, environmental sound is easy to handle, and is nontoxic etc.It further mixes well with acetone when being used as solvent, because the two dissolving mutually well, polymkeric substance precipitates effectively owing to the low dissolving power of final acetone-water system and separates out simultaneously.
If water as precipitation agent, then can be added a small amount of organic or inorganic compound, effect of surface tension agent or complexing agent, so that by for example promoting the influence that increases purification process efficient that separates of precipitation process or liquid phase and solid phase.
The following example explanation the present invention.
Material
Use 53 moles of %D, the multipolymer of L-rac-Lactide and 47 moles of % glycollide in the experiment.Rough polymkeric substance comprises the residual monomer of 1.16wt.%.
In the experiment in addition polymkeric substance is dissolved in acetone (acetone-polymeric blends A-D) (referring to Table I)
Table I
| Mixture | Wt.% concentration |
| A | 3.9 |
| B | 6.0 |
| C | 8.0 |
| D | 10.5 |
Precipitation
In settling step, as precipitation agent, acetone is as solvent with water.Acetone-polymers soln A-D is added in IKA Ultra Turrax UTL 25 homogenizers of being furnished with the S25KV-25-G-IL diverting device.Water is main process flow, and the mixing section of flowing through.In mixing section, the rotor-stator system produces the shear field.Polymers soln is added near the shear field the water.Term " near " be meant the mixing tank part that is positioned at or approaches to cause shearing force, promptly be positioned at shearing force and be at least 25% position of the maximum shear stress of mixing tank.Can change the water yield (flow) of adding in polymkeric substance-acetone soln, thereby obtain optimum.To precipitate slurry and send in the whizzer, thus the polymer precipitation in the collection filter bag.Impure current flow out and are discharged from from whizzer.In the whizzer of slowly rotation, make water clean filter cake, remove big quantity of fluid thereby after this strengthen speed of rotation.Remaining filter cake ground and material is dry and measure residual monomer content by GC in vacuum chamber under 25-30 ℃.
Viscosity measurement
Use Ubbelohde viscometer (Schott
Type II) the kinematic viscosity that measurement has the various polymkeric substance-acetone mixture of different wt.% polymkeric substance according to standard step under 25 ℃.Draw the graphic representation of the logarithmic value of, obtain two and have intersection point C the logarithmic value of concentration (wt.%)
CritStraight line.
Under 25 ℃, in chloroform, measure (Schott equally
Type OC) limiting viscosity of polymkeric substance itself
GC measures
Material and facility:
Use is furnished with the Var ian Star3600VX gas chromatograph of fused silica column and flame ionization detector and analyzes residual monomer.Polymer samples is dissolved in the chloroform, uses the 1-octanol as interior mark (the 1g1-octanol is dissolved in the 100ml solvent).Content by monomeric calculated by peak area residual monomer.
The Gc condition:
Injector temperature: 180 ℃
Detector temperature: 300 ℃
Initial column temperature: 150 ℃
Retention time: 2 minutes
Final column temperature: 200 ℃
Retention time: 3 minutes
Speed: 10 ℃/min
Carrier gas stream: 1.5mL/min
Pressure: 0.552 crust
Division: 60
According to the result of standardized solution, can use following formula to measure the response factor R of monomer than the 1-octanol:
R=(area of amount/M of M)/(area of amount/IS of IS)
Wherein:
The amount of M=monomeric addition (mole)
The area at the area of M=monomer peak
The addition (mole) of the amount of IS=interior mark (1-octanol)
The area at the area of IS=interior mark peak
Because peak area is relevant with the mole number of material, can use following formula to calculate monomeric amount:
Monomeric amount (%w/w)=
The amount (mg) of the area .fwM.100/ sample of (area of amount/IS of IS) .R.M
Wherein
The amount of IS=interior target addition (mmole)
The area at the area of IS=interior mark peak
The R=response factor
The area at the area of M=monomer peak
The monomeric molecular weight of fwM=(g/mole)
The result
| Solution | Flow velocity polymkeric substance/water (vol/vol) | Log C crit | Log C | Residual monomer content (wt%) | Be positioned at claim 1-3 |
| A | 1:8.6 | -1.40 | -1.41 | Bd1* | 3 |
| A | 1:14.2 | -1.40 | -1.41 | Bd1 | 3 |
| A | 1:15.1 | -1.40 | -1.41 | Bd1 | 3 |
| A | 1:26.8 | -1.40 | -1.41 | Bd1 | 3 |
| B | 1:34.6 | -1.40 | -1.22 | Bd1 | 2 |
| B | 1:10.6 | -1.40 | -1.22 | Bd1 | 2 |
| B | 1:16.1 | -1.40 | -1.22 | Bd1 | 2 |
| B | 1:15.7 | -1.40 | -1.22 | Bd1 | 2 |
| B | 1:26.3 | -1.40 | -1.22 | Bd1 | 2 |
| B | 1:47.8 | -1.40 | -1.22 | Bd1 | 2 |
| C | 1:15.3 | -1.40 | -1.10 | Bd1 | 1 |
| C | 1:16.4 | -1.40 | -1.10 | 0.01 | 1 |
| C | 1:23.9 | -1.40 | -1.10 | 0.01 | 1 |
| C | 1:47.8 | -1.40 | -1.10 | 0.07 | 1 |
| C | 1:65.2 | -1.40 | -1.10 | Bd1 | 1 |
| D | 1:26 | -1.40 | -0.98 | 0.03 | Relatively |
| D | 1:46 | -1.40 | -0.98 | 0.08 | Relatively |
| D | 1:97 | -1.40 | -0.98 | 0.08 | Relatively |
* Bd1=is lower than the limit of detection of GC
Claims (8)
1, a kind of method from the residual monomer purification of resorbable polymers comprises that adding described polymkeric substance is dissolved in the solution in the solvent and adds precipitation agent to precipitate this polymkeric substance in mixing section, and the concentration that it is characterized in that polymkeric substance in the solution is log C
Crit± 0.3 log unit, wherein C
CritIt is threshold concentration.
2, according to the process of claim 1 wherein that the concentration of polymkeric substance is log C in the solution
Crit± 0.2 log unit.
3, according to the process of claim 1 wherein that the concentration of polymkeric substance is log C in the solution
Crit± 0.1 log unit.
4, according to each method of claim 1-3, wherein with polymer purification to comprising the residual monomer that some are lower than the vapor-phase chromatography limit of detection.
5, according to each method of claim 1-4, wherein solvent is an acetone, and precipitation agent is a water.
6, according to each method of claim 1-5, wherein polymkeric substance comprises at least a glycollide, own lactide, L-rac-Lactide, D-rac-Lactide, the D of deriving from, the monomeric part of L-rac-Lactide and Study of Meso-Lactide.
7, according to the method for claim 6, wherein the limiting viscosity of polymkeric substance in 25 ℃ chloroform is 0.1-6dl/g.
8, according to each method of claim 1-7, wherein precipitation agent is a water, and it adds near the shearing force of the mixing tank that causes the water-soluble polymers slurry flow.
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP06101101 | 2006-01-31 | ||
| EP06101101.1 | 2006-01-31 | ||
| PCT/EP2007/050731 WO2007088135A1 (en) | 2006-01-31 | 2007-01-25 | Method for the purification of resorbable polymers from residual monomers |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN101400708A true CN101400708A (en) | 2009-04-01 |
| CN101400708B CN101400708B (en) | 2012-02-01 |
Family
ID=36609379
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN2007800071700A Active CN101400708B (en) | 2006-01-31 | 2007-01-25 | Method for the purification of resorbable polymers from residual monomers |
Country Status (7)
| Country | Link |
|---|---|
| EP (1) | EP1979381B1 (en) |
| JP (1) | JP2009525372A (en) |
| CN (1) | CN101400708B (en) |
| AT (1) | ATE541866T1 (en) |
| BR (1) | BRPI0707404B1 (en) |
| ES (1) | ES2378835T3 (en) |
| WO (1) | WO2007088135A1 (en) |
Cited By (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103421172A (en) * | 2012-05-23 | 2013-12-04 | 上海现代药物制剂工程研究中心有限公司 | Purification technique of biodegradable polyesters |
| CN105492503A (en) * | 2013-08-29 | 2016-04-13 | 赢创罗姆有限公司 | Process for preparing a bio-resorbable polyester in the form of a powder |
| CN105026458B (en) * | 2013-02-26 | 2017-06-16 | 益普生制药股份有限公司 | The method for purifying polyester |
Families Citing this family (4)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP5320758B2 (en) * | 2008-02-04 | 2013-10-23 | 東洋紡株式会社 | Polylactic acid resin melt |
| JP5959728B2 (en) * | 2013-04-11 | 2016-08-02 | 三井化学株式会社 | Method for producing lactic acid-glycolic acid copolymer or salt thereof |
| WO2016075071A1 (en) * | 2014-11-14 | 2016-05-19 | Evonik Röhm Gmbh | Process for preparing a bio-resorbable polyester in particulate form |
| JP2019167402A (en) * | 2018-03-22 | 2019-10-03 | 三井化学株式会社 | Manufacturing method of powder containing lactic acid-glycolic acid copolymer |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60248727A (en) * | 1984-05-23 | 1985-12-09 | Kuraray Co Ltd | Purification of delta-valerolactone polymer |
| JP2551756B2 (en) * | 1985-05-07 | 1996-11-06 | 武田薬品工業株式会社 | Polyoxycarboxylic acid ester and method for producing the same |
| DE3641692A1 (en) * | 1986-12-06 | 1988-06-09 | Boehringer Ingelheim Kg | CATALYST-FREE RESORBABLE HOMOPOLYMERS AND COPOLYMERS |
| DE3708916A1 (en) * | 1987-03-19 | 1988-09-29 | Boehringer Ingelheim Kg | METHOD FOR CLEANING RESORBABLE POLYESTERS |
| DE3937272A1 (en) * | 1989-11-09 | 1991-05-16 | Boehringer Ingelheim Kg | NEW COPOLYMERS FROM TRIMETHYLENE CARBONATE AND OPTICALLY INACTIVE LACTIDS |
| JP3200706B2 (en) * | 1990-04-13 | 2001-08-20 | 武田薬品工業株式会社 | Biodegradable polymer |
| CA2309575A1 (en) * | 2000-05-26 | 2001-11-26 | James E. Guillet | Internally cross-linked macromolecules |
-
2007
- 2007-01-25 WO PCT/EP2007/050731 patent/WO2007088135A1/en active Application Filing
- 2007-01-25 AT AT07712113T patent/ATE541866T1/en active
- 2007-01-25 JP JP2008552783A patent/JP2009525372A/en active Pending
- 2007-01-25 ES ES07712113T patent/ES2378835T3/en active Active
- 2007-01-25 EP EP07712113A patent/EP1979381B1/en active Active
- 2007-01-25 BR BRPI0707404-2A patent/BRPI0707404B1/en active IP Right Grant
- 2007-01-25 CN CN2007800071700A patent/CN101400708B/en active Active
Cited By (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN103421172A (en) * | 2012-05-23 | 2013-12-04 | 上海现代药物制剂工程研究中心有限公司 | Purification technique of biodegradable polyesters |
| CN103421172B (en) * | 2012-05-23 | 2016-01-20 | 上海现代药物制剂工程研究中心有限公司 | A kind of purifying process of biodegradable polyesters |
| CN105026458B (en) * | 2013-02-26 | 2017-06-16 | 益普生制药股份有限公司 | The method for purifying polyester |
| CN105492503A (en) * | 2013-08-29 | 2016-04-13 | 赢创罗姆有限公司 | Process for preparing a bio-resorbable polyester in the form of a powder |
| CN105492503B (en) * | 2013-08-29 | 2018-02-09 | 赢创罗姆有限公司 | The preparation method of powder type Bioabsorbable Polyesters |
Also Published As
| Publication number | Publication date |
|---|---|
| BRPI0707404A2 (en) | 2011-05-03 |
| EP1979381B1 (en) | 2012-01-18 |
| EP1979381A1 (en) | 2008-10-15 |
| BRPI0707404B1 (en) | 2018-05-29 |
| WO2007088135A1 (en) | 2007-08-09 |
| ATE541866T1 (en) | 2012-02-15 |
| BRPI0707404A8 (en) | 2017-07-11 |
| JP2009525372A (en) | 2009-07-09 |
| CN101400708B (en) | 2012-02-01 |
| ES2378835T3 (en) | 2012-04-18 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN101400708B (en) | Method for the purification of resorbable polymers from residual monomers | |
| JP2010506965A (en) | Preparation of biodegradable polyester with low burst characteristics by supercritical fluid extraction | |
| US8076448B2 (en) | Preparation of biodegradable polyesters with low-burst properties by supercritical fluid extraction | |
| Huynh et al. | Biodegradable pH/temperature-sensitive oligo (β-amino ester urethane) hydrogels for controlled release of doxorubicin | |
| Wang et al. | Preparation and characterization of pH-sensitive hydrogel for drug delivery system | |
| Wee et al. | New poly [(r)‐3‐hydroxybutyrate‐co‐4‐hydroxybutyrate](P3HB4HB)‐based thermogels | |
| Appel et al. | Toward biodegradable nanogel star polymers via organocatalytic ROP | |
| He et al. | Synthesis and physicochemical characterization of biodegradable and pH‐responsive hydrogels based on polyphosphoester for protein delivery | |
| US9926412B2 (en) | Enhancing the physical properties of semi-crystalline polymers via solid-state shear pulverization | |
| Nguyen et al. | Molecular design of novel pH/temperature-sensitive hydrogels | |
| Yang et al. | Synthesis and characterization of amphiphilic block copolymer of polyphosphoester and poly (l‐lactic acid) | |
| US20070179276A1 (en) | Method for the purification of resorbable polymers from residual monomers | |
| Marlina et al. | Raman spectra of polyethylene glycol/cellulose acetate butyrate biopolymer blend | |
| Williams et al. | Degradable graft copolymers by ring-opening and reverse addition–fragmentation chain transfer polymerization | |
| Kohli et al. | Preparation, characterization and evaluation of poly (lactide–co–glycolide) microspheres for the controlled release of zidovudine | |
| Yoo et al. | Novel pH and temperature-sensitive block copolymers: Poly (ethylene glycol)-b-poly (ε-caprolactone)-b-poly (β-amino ester) | |
| Ouchi et al. | Synthesis of poly (l‐lactide)‐grafted pullulan through coupling reaction between amino group end‐capped poly (l‐lactide) and carboxymethyl pullulan and its aggregation behavior in water | |
| Bishara et al. | Stereocomplexes of Triblock Poly (lactide‐PEG2000‐lactide) as Carrier of Drugs | |
| Beckham | Ring polymers: effective isolation and unique properties | |
| Chen et al. | Self-assembly and drug delivery behaviors of a novel thermo-sensitive block glycopolymer | |
| Latere Dwan'Isa et al. | Spontaneously self-assembled micelles from poly (ethylene glycol)-b-poly (ɛ-caprolactone-co-trimethylene carbonate) for drug solubilization | |
| Abdel-Hady et al. | Miscibility and crystallization behavior of poly (3-hydroxybutyrate) and poly (ethylene glycol) blends studied by positron annihilation spectroscopy | |
| Bear et al. | Biosynthetic stereocopolymer of 3-methylmalic acid as hydrolyzable and biocompatible polyester for temporary therapeutic applications | |
| Ding et al. | Micelle formation from hydrophobically end-capped poly (ethylene oxide) and its application for delivery of poorly water-soluble drug | |
| Du et al. | Synthesis and Self-Assembly Study of Biodegradable Amphiphilic Triblock Copolymers with PEG Block |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| C06 | Publication | ||
| PB01 | Publication | ||
| C10 | Entry into substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| C14 | Grant of patent or utility model | ||
| GR01 | Patent grant |